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Chapter: Basic & Clinical Pharmacology : Cancer Chemotherapy

Lung Cancer

Lung cancer is divided into two main histopathologic subtypes, non-small cell and small cell.


Lung cancer is divided into two main histopathologic subtypes, non-small cell and small cell. Non-small cell lung cancer (NSCLC) makes up about 75–80% of all cases of lung cancer, and this group includes adenocarcinoma, squamous cell cancer, and large cell cancer, while small cell lung cancer (SCLC) makes up the remain-ing 20–25%. When NSCLC is diagnosed in an advanced stage with metastatic disease, the prognosis is extremely poor, with a median survival of about 8 months. It is clear that prevention (pri-marily through avoidance of cigarette smoking) and early detection remain the most important means of control. When diagnosed at an early stage, surgical resection results in patient cure. Moreover, recent studies have shown that adjuvant platinum-based chemo-therapy provides a survival benefit in patients with pathologic stage IB, II, and IIIA disease. However, in most cases, distant metastases have occurred at the time of diagnosis. In certain instances, radia-tion therapy can be offered for palliation of pain, airway obstruc-tion, or bleeding and to treat patients whose performance status would not allow for more aggressive treatments.

In patients with advanced disease, systemic chemotherapy is gen-erally recommended. Combination regimens that include a plati-num agent (“platinum doublets”) appear superior to non-platinum doublets, and either cisplatin or carboplatin are appropriate platinum agents for such regimens. For the second drug, paclitaxel and vino-relbine appear to have activity independent of histology, while the antifolate pemetrexed should be used for non-squamous cell cancer, and gemcitabine for squamous cell cancer. For patients with good performance status and those with non-squamous histology, the combination of the anti-VEGF antibody bevacizumab with carbo-platin and paclitaxel is a standard treatment option. In patients deemed not to be appropriate candidates for bevacizumab therapy and those with squamous cell histology, a platinum-based chemo-therapy regimen in combination with the anti-EGFR antibody cetuximab is a reasonable treatment strategy. Maintenance chemo-therapy with pemetrexed is now used in patients with non-squamous NSCLC whose disease has not progressed after four cycles of plati-num-based first-line chemotherapy. Finally, first-line therapy with an EGFR tyrosine kinase inhibitor, such as erlotinib or gefitinib, sig-nificantly improves outcomes in NSCLC patients with sensitizing EGFR mutations.

Small cell lung cancer is the most aggressive form of lung cancer, and it is exquisitely sensitive, at least initially, to platinum-based combination regimens, including cisplatin and etoposide or cisplatin and irinotecan. When diagnosed at an early stage, this disease is potentially curable using a combined modality approach of chemo-therapy and radiation therapy. Unfortunately, drug resistance eventu-ally develops in nearly all patients with extensive disease. The topoisomerase I inhibitor topotecan is used as second-line mono-therapy in patients who have failed a platinum-based regimen.

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